Fluorinated compounds have a wide range of applications, for instance as building blocks in drug synthesis in the pharmaceutical industry. The incorporation of a fluoro substituent α- to a carbonyl group is now well established, with several reagent-based enantioselective fluorinations of enolates or silyl enol ethers having been reported; see for example Differding, E.; Lang, R. W. Tetrahedron Lett. 1988, 29, 6087-6090.
More recently, it has been found that transition metal complexes and small organic molecules are efficient catalysts for the formation of enantioenriched α-fluorinated carbonyl derivatives; see for example Ma, J.-A.; Cahard, D. Chem. Rev. 2004, 104, 6119-6146.
By way of contrast, few synthetic routes have been developed for the preparation of homochiral fluorinated building blocks other than α-fluorinated carbonyl compounds. For example, a general methodology for the preparation of enantiopure β-fluorinated γ,δ-unsaturated carboxylic acids with a stereogenic fluorinated allylic carbon has yet to be developed. Various alternative syntheses of enantioenriched β-fluorinated carboxylic acids not featuring an allylic fluoride are known, for example: Kollonitsch, J.; Marburg, S.; Perkins, L. M. J. Org. Chem. 1979 44, 771-777.
It has also been reported that non-aromatic organosilanes, such as vinylsilanes, allylsilanes and allenylmethylsilanes, react with 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoro-borate) (Selectfluor™) to give structurally diverse fluorinated compounds. Using this methodology for electrophilic fluorination, fluoroalkenes, difluorinated amides, ethers or alcohols, allylic fluorides and fluorodienes have been made available; see for example Gouverneur, V.; Greedy, B. Chem. Eur. J. 2002, 8, 766-771.
Routes to allylic fluorides are rare and known approaches based on the use of nucleophilic sources of fluorine reacting with allylic alcohols suffer from problems of double bond transposition. The present invention provides an alternative route to allylic fluorides based on the electrophilic fluorodesilylation of allylsilanes using a source of electrophilic fluorine.